[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome

  • Report
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Purpose

Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer.

Methods

DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort.

Results

We found that six genes were differentially methylated in the test samples, of which four were linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-1299, ANKRD2). Three of these genes were also found to be significantly differentially methylated in the validation cohort, indicating that the observed effects are genuine.

Conclusion

Tissue ischaemia during normal surgical removal of tumour can cause epigenetic changes. Based on these results, we conclude that the impact of sampling procedures in clinical epigenetic studies should be considered and discussed, particularly after inducing hypoxia/ischaemia, which occurs in most oncological surgery procedures through which tissues are collected for translational research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. A. Ferraro, Primary chromatin structures and their implications in cancer development. Cell Oncol 39, 195–210 (2016). doi:10.1007/s13402-016-0276-6

  2. V. Taucher, H. Mangge, J. Haybaeck, Non-coding RNAs in pancreatic cancer: challenges and opportunities for clinical application. Cell Oncol 39, 295–318 (2016). doi:10.1007/s13402-016-0275-7

  3. M. Vitiello, A. Tuccoli, L. Poliseno, Long non-coding RNAs in cancer: implications for personalized therapy. Cell Oncol 38, 17–28 (2015). doi:10.1007/s13402-014-0180-x

  4. K. Sharpe, G.D. Stewart, A. Mackay, C. Van Neste, C. Rofe, D. Berney, I. Kayani, A. Bex, E. Wan, F.C. O’Mahony, M. O’Donnell, S. Chowdhury, R. Doshi, C. Ho-Yen, M. Gerlinger, D. Baker, N. Smith, B. Davies, A. Sahdev, E. Boleti, T.D. Meyer, W.V. Criekinge, L. Beltran, Y.-J. Lu, D.J. Harrison, A.R. Reynolds, T. Powles, The effect of VEGF-targeted therapy on biomarker expression in sequential tissue from patients with metastatic clear cell renal cancer. Clin Cancer Res 19, 6924–6934 (2013). doi:10.1158/1078-0432.ccr-13-1631

    Article  CAS  PubMed  Google Scholar 

  5. G.D. Stewart, F.C. O’Mahony, A. Laird, L. Eory, A.L.R. Lubbock, A. Mackay, J. Nanda, M. O’Donnell, P. Mullen, S.A. McNeill, A.C. Riddick, D. Berney, A. Bex, M. Aitchison, I.M. Overton, D.J. Harrison, T. Powles, Sunitinib treatment exacerbates intratumoral heterogeneity in metastatic renal cancer. Clin Cancer Res 21, 4212–4223 (2015). doi:10.1158/1078-0432.ccr-15-0207

    Article  CAS  PubMed  Google Scholar 

  6. G.D. Stewart, F.C. O’Mahony, T. Powles, A.C.P. Riddick, D.J. Harrison, D. Faratian, What can molecular pathology contribute to the management of renal cell carcinoma? Nature Rev Urol 8, 255–265 (2011). doi:10.1038/nrurol.2011.43

    Article  CAS  Google Scholar 

  7. Confederation of Cancer Biobanks: Biobank Quality Standard - Collecting, Storing and Providing Human Biological Material and Data for Research (2014) http://ccb.ncri.org.uk/wp-content/uploads/2014/03/Biobank-quality-standard-Version-1.pdf

  8. M.B. Freidin, N. Bhudia, E. Lim, A.G. Nicholson, W.O. Cookson, M.F. Moffatt, Impact of collection and storage of lung tumor tissue on whole genome expression profiling. J Mol Diagn 14, 140–148 (2012). doi:10.1016/j.jmoldx.2011.11.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Q. Liu, L. Liu, Y. Zhao, J. Zhang, D. Wang, J. Chen, Y. He, J. Wu, Z. Zhang, Z. Liu, Hypoxia induces genomic DNA demethylation through the activation of HIF-1a and transcriptional upregulation of MAT2A in hepatoma cells. Mol Cancer Ther 10, 1113–1123 (2011). doi:10.1158/1535-7163.mct-10-1010

  10. W.G. Kaelin Jr., The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer 8, 865–873 (2008). doi:10.1038/nrc2502

    Article  CAS  PubMed  Google Scholar 

  11. R. Motzer, M. Michaelson, B. Redman, G. Hudes, G. Wilding, R. Figlin, M. Ginsberg, S. Kim, C. Baum, S. DePrimo, J. Li, C. Bello, C. Theuer, D. George, B. Rini, Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24, 16–24 (2006). doi:10.1200/JCO.2005.02257

    Article  CAS  PubMed  Google Scholar 

  12. N.W. Liu, T. Sanford, R. Srinivasan, J.L. Liu, K. Khurana, O. Aprelikova, V. Valero, C. Bechert, R. Worrell, P.A. Pinto, Y. Yang, M. Merino, W.M. Linehan, G. Bratslavsky, Impact of ischemia and procurement conditions on gene expression in renal cell carcinoma. Clin Cancer Res 19, 42–49 (2013). doi:10.1158/1078-0432.ccr-12-2606

    Article  PubMed  Google Scholar 

  13. G. Stewart, T. Powles, C. Van Neste, A. Meynert, F. O’Mahony, A. Laird, D. Deforce, F. Van Nieuwerburgh, G. Trooskens, W. Van Criekinge, T. De Meyer, D.J. Harrison, Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer. Oncotarget 7, 25241–25250 (2016). doi:10.18632/oncotarget.8308

    PubMed  PubMed Central  Google Scholar 

  14. T. De Meyer, E. Mampaey, M. Vlemmix, S. Denil, G. Trooskens, J.-P. Renard, S. De Keulenaer, P. Dehan, G. Menschaert, W. Van Criekinge, Quality evaluation of methyl binding domain based kits for enrichment DNA-methylation sequencing. PLoS One 8, 59068 (2013). doi:10.1371/journal.pone.0059068

    Article  Google Scholar 

  15. Biobix: Map of the Human Methylome. http://www.biobix.be/map-of-the-human-methylome/mhm-version-2/

  16. S. Hicks, R. Irizarry, Quantro: a data-driven approach to guide the choice of an appropriate normalization method. Genome Biol 16, 117 (2015). doi:10.1186/s13059-015-0679-0

    Article  PubMed  PubMed Central  Google Scholar 

  17. C.W. Law, Y. Chen, W. Shi, G.K. Smyth, Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol 15, 29 (2014). doi:10.1186/gb-2014-15-2-r2

    Article  Google Scholar 

  18. M. Esteller, Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 16, 50–59 (2007). doi:10.1093/hmg/ddm018

    Article  Google Scholar 

  19. P.-J. Volders, K. Verheggen, G. Menschaert, K. Vandepoele, L. Martens, J. Vandesompele, P. Mestdagh, An update on LNCipedia: a database for annotated human lncRNA sequences. Nucleic Acids Res 43, 174–180 (2014). doi:10.1093/nar/gku1060

    Article  Google Scholar 

  20. M.R. D’Apice, A. Novelli, A. di Masi, M. Biancolella, A. Antoccia, F. Gullotta, N. Licata, D. Minella, B. Testa, A.M. Nardone, G. Palmieri, E. Calabrese, L. Biancone, C. Tanzarella, M. Frontali, F. Sangiuolo, G. Novelli, F. Pallone, Deletion of REXO1L1 locus in a patient with malabsorption syndrome, growth retardation, and dysmorphic features: a novel recognizable microdeletion syndrome? BMC Med Genet 16, 20 (2015). doi:10.1186/s12881-015-0164-3

    Article  PubMed  PubMed Central  Google Scholar 

  21. A. Greijer, P. van der Groep, D. Kemming, A. Shvarts, G. Semenza, G. Meijer, M. van de Wiel, J. Belien, P. van Diest, E. van der Wall, Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (hif-1). J Pathol 206, 291–304 (2005). doi:10.1002/path.1778

    Article  CAS  PubMed  Google Scholar 

  22. H. Wu, G. Chen, K.R. Wyburn, J. Yin, P. Bertolino, J.M. Eris, S.I. Alexander, A.F. Sharland, S.J. Chadban, Tlr4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 117, 2847–2859 (2007). doi:10.1172/jci31008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Z. Liu, W. He, J. Gao, J. Luo, X. Huang, C. Gao, Computational prediction and experimental validation of a novel synthesized pan-pim inhibitor pi003 and its apoptosis-inducing mechanisms in cervical cancer. Oncotarget 6, 8019–8035 (2015). doi:10.18632/oncotarget.3139

    Article  PubMed  PubMed Central  Google Scholar 

  24. M. Safran, I. Dalah, J. Alexander, N. Rosen, T.I. Stein, M. Shmoish, N. Nativ, I. Bahir, T. Doniger, H. Krug, A. Sirota-Madi, T. Olender, Y. Golan, G. Stelzer, A. Harel, D. Lancet, GeneCards version 3: the human gene integrator. Database (Oxford) 2010, baq020 (2010). doi:10.1093/database/baq020

    Article  Google Scholar 

  25. M.K. Miller, M.-L. Bang, C.C. Witt, D. Labeit, C. Trombitas, K. Watanabe, H. Granzier, A.S. McElhinny, C.C. Gregorio, S. Labeit, The muscle ankyrin repeat proteins: carp, ankrd2/arpp and darp as a family of titin filament-based stress response molecules. J Mol Biol 333, 951–964 (2003). doi:10.1016/j.jmb.2003.09.012

    Article  CAS  PubMed  Google Scholar 

  26. M. Band, A. Joel, A. Avivi, The muscle ankyrin repeat proteins are hypoxia-sensitive: in vivo mrna expression in the hypoxia-tolerant blind subterranean mole rat, spalax ehrenbergi. J Mol Evol 70, 1–12 (2009). doi:10.1007/s00239-009-9306-6

    Article  PubMed  Google Scholar 

Download references

Author’s contributions

Conception and design: DJH, AL, GDS, TDM, TP. Development of methodology: CVN, GDS, DJH, TP, TDM. Acquisition of data (acquired and managed patients, provided facilities, etc.): GDS, FOM, AL, DJH, TP. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): CVN, TDM, GDS, DJH. Writing, review, and/or revision of the manuscript: CVN, AL, FOM, WVC, DD, FVN, TP, DJH, GDS, TDM. Study supervision: GDS, DJH, TDM, WVC.

Author information

Authors and Affiliations

  1. Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium

    Christophe Van Neste, Dieter Deforce & Filip Van Nieuwerburgh

  2. Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium

    Christophe Van Neste

  3. Edinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK

    Alexander Laird, Fiach O’Mahony, David J. Harrison & Grant D. Stewart

  4. Scottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC), Edinburgh, UK

    Alexander Laird, Fiach O’Mahony, David J. Harrison & Grant D. Stewart

  5. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK

    Alexander Laird

  6. Biobix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modeling, Statistics and Bioninformatics, Ghent University, Coupure Links 653, 9000, Ghent, Belgium

    Wim Van Criekinge & Tim De Meyer

  7. Renal Cancer Unit, The Royal Free Hospital, London, NW3 2QG, UK

    Thomas Powles

  8. Centre for Experimental Cancer Medicine, Bart’s Cancer Institute, Queen Mary University of London, London, EC1A 7BE, UK

    Thomas Powles

  9. School of Medicine, University of St Andrews, Edinburgh, St Andrews, KY16 9TF, UK

    David J. Harrison

Authors
  1. Christophe Van Neste
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Laird
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fiach O’Mahony
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wim Van Criekinge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dieter Deforce
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Filip Van Nieuwerburgh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Powles
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David J. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Grant D. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tim De Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Harrison.

Ethics declarations

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Permission to use tissue was obtained from local research ethics committees.

Funding

This work was supported by the Chief Scientist Office, Scotland (ETM37; GDS, DJH), Cancer Research UK (Experimental Cancer Medicine Centre; TP, London, DJH, Edinburgh), Medical Research Council (AL, DJH), Royal College of Surgeons of Edinburgh Robertson Trust (AL), Melville Trust AL), Renal Cancer Research Fund (GDS, DJH), Kidney Cancer Scotland (GDS) and an educational grant from Pfizer (TP). CVN and TDM were funded by Ghent University Multidisciplinary Research Partnership ‘Bioinformatics: from nucleotides to networks’.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all participants included in the study.

Additional information

Tim De Meyer and Grant D. Stewart contributed equally to this work.

Electronic supplementary material

ESM 1

(PDF 20 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Van Neste, C., Laird, A., O’Mahony, F. et al. Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome. Cell Oncol. 40, 293–297 (2017). https://doi.org/10.1007/s13402-016-0313-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-016-0313-5

Keywords

Search

Navigation